In the last decade, per capita prescription drug use in the U.S. more than doubled. Americans over 65 now consume an average of 28 prescriptions per year. My preliminary analyses show that in 2007, the average Medicare Part D enrollee received more than 43 30-day prescription fills. While polypharmacy is increasingly common, research on this topic is surprisingly sparse. Evidence demonstrates important adverse outcomes associated with polypharmacy and suggests that older adults may be particularly susceptible to medication-associated adverse outcomes due to their relative frailty, chronicity of treatment and multiple morbidities. Medications are credited with enhanced quality and length of life and averting use of other health services, but as drug use expands, the challenge is to achieve balance between benefits and risks. As a junior investigator, my long-term career goal is to become a leading researcher on causes and consequences of polypharmacy among older adults. The career development aims of this proposal are: (1) to develop the experience, skills, and advanced statistical methods and models necessary for effective and efficient analysis of merged claims from Medicare parts A, B and D; and (2) to develop expertise, pilot data, and collaborative relationships necessary to advance toward independent funding and a career as a leader in the field of geriatric pharmacoepidemiology. To advance these career aims, I propose a mentored study of fractures associated with exposure to multiple medication classes individually associated with fracture. The specific research aims are: (1) to characterize fracture-promoting prescription drug use among Medicare Part D enrollees; (2) to explore individual and system-specific determinants of prescription drug use intensity; and (3) to quantify the association between fracture-promoting polypharmacy and fracture. This topic directly addresses high-priority research areas of the NIA Geriatrics Branch, specifically, effects of comorbidity and polypharmacy and multifactorial geriatric syndromes; and will lead to R01 applications for continued study of the causes and consequences of geriatric polypharmacy.